The Genetic Origins of Cleft Lip

The first common genetic variant strongly associated with cleft lip has been identified in a study published online in Nature Genetics. The finding highlights a previously unknown developmental pathway underlying the origin of this birth defect.

Cleft lips or palates occur in approximately 1 of every 700 live births, and are characterized by facial abnormalities. Jeffrey Murray and colleagues previously showed that mutations in the gene IRF6 are associated with a rare clefting disorder called Van der Woude syndrome, although the specific variant that is responsible for the cleft remained unknown. They now identify a genetic variant associated with risk of the more common, nonsydnromic form of cleft lip. This variant promotes expression of IRF6 in the mouse embryo at sites where the facial areas fuse, and is activated by another gene product involved in facial development, AP-2alpha.

Although evidence is mounting that 'regulatory' variants have an important role in the genetic basis of common, complex disorders, the variant identified in this study is one of the first clear examples.